Abstract
Recent experiments have shown that gene repression can be correlated with relocation of genes to heterochromatin-rich silent domains. Here, we investigate whether nuclear architecture and spatial positioning can contribute directly to the transcriptional activity of a genetic locus in Saccharomyces cerevisiae. By disassembling telomeric silent domains without altering the chromatin-mediated silencing machinery, we show that the transcriptional activity of silencer–reporter constructs depends on intranuclear position. This demonstrates that telomeric silent domains are actively involved in transcriptional silencing. Employing fluorescent in situ hybridization (FISH) in combination with genetic assays, we demonstrate that telomeres control the establishment of transcriptional states by reversible partitioning with the perinuclear silencing domains. Anchoring telomeres interferes with their ability to assume an active state, whereas disassembly of silencing domains prevents telomeres from assuming a repressed state. Our data support a model in which domains of enriched transcriptional regulators allow genes to determine transcriptional states by spatial positioning.
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Acknowledgements
We are indebted to R. Sternglanz and D. Zappulla (Stony Brook University, NY), K. Nasmyth (University of Vienna), E. Fabre (Institut Pasteur, Paris) and G. Fourel (ENS, Lyon, France) for their kind gift of strains and plasmids. We thank V. Geli (CNRS, Marseille, France) for critical reading of the manuscript. F. F. is supported by a fellowship from Association Nationale de la Recherche contre le SIDA and V. G. is supported by a fellowship from the French Ministry of Research. Work was supported in part by a grant from the Action pour la Recherche contre le Cancer (ARC).
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Supplementary figures
Supplemental figure 1. Deletion of NUP60 has no effect on protein import/export. (PDF 2181 kb)
Supplemental figure 2. Deletion of the C terminal part of Nup145p or NUP60 releases telomeres from their perinuclear localization.
Supplemental figure 3. Effect of MLP1 or MLP2 deletion on telomere clustering and localization.
Supplemental figure 4. Deletion of MLP1 or YKU70 leads to partial release of the Sir3p-GFP protein from the nuclear matrix.
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Feuerbach, F., Galy, V., Trelles-Sticken, E. et al. Nuclear architecture and spatial positioning help establish transcriptional states of telomeres in yeast. Nat Cell Biol 4, 214–221 (2002). https://doi.org/10.1038/ncb756
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DOI: https://doi.org/10.1038/ncb756
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